*from MEDCSCAPE
" AP26113 is a second-generation ALK and ROS1 inhibitor that seems
in vitro to also have some activity against the activating epidermal
growth factor receptor (EGFR) mutations and T790M."..." We are showing the results from the phase 1 dose-escalation study[1] across a broad dose range.
In the ALK patients, most of whom have not responded to crizotinib,
we are seeing fantastic activity: a 75% response rate in patients who
had progressed on crizotinib. That is occurring at doses from 60 mg all
the way up to 240 mg. They are now taking 180 mg forward as the
recommended phase 2 dose. It seems to be very well tolerated. One case
of pneumonitis occurred at one of the lower doses, and some other
patients with low performance status did relatively badly. But
after pausing, tightening up on the inclusion criteria, and adding extra
patients to those cohorts, "
*"Other monoclonal antibodies being evaluated for relapse and refractory indolent non Hodgkin Lymphoma include Epratuzumab (Anti-CD22) Galiximab (anti-CD80), Dacetuzumab (anti-CD40) and a number of humanized anti CD20 monoclonal antibodies." (ASCO)
*"High levels of soluble IL-2 Receptors (>5 times normal) are present in the sera of almost all patients with Hairy cell leukemia " (Hagop Kantargian and Susan Obrien) The disease is characterized by Cytopenia and impaired skin test reactivity. inversion of CD4/CD8.
This the driver force in this disease? or is-it a consequence of epigenic phenomena? Insurer will fight you if you try to make this a biomarker? And we forgot to measure the METALLOPROTEINASES HERE!
The point is that the response to 2-CDA, Pentostatin, and Interferon suggest the IL-2Ra is most likely causative since these agents have profound epigenetic effects.
BY THE WAY, EPRATUZUMAB IS AN ANTI-CD22, WHICH IS ALSO PRESENT IN HAIRY CELL! (proof of concept)
Sunday, August 4, 2013
Saturday, August 3, 2013
FAILURE IN CURRENT ONCOLOGY PRACTICE: THE CANCER SURVIVOR STORY
"The American Association for Cancer Research has released its second Annual Report on Cancer Survivorship in the United States. The report, published in the AACR’s journal Cancer Epidemiology, Biomarkers & Prevention,
shows that as of January 2012, there were approximately 13.7 million
cancer survivors in the United States, a number that is expected to rise
by 31 percent to 18 million by 2022."(NCSD)
It is quite apparant that one of the shame in Oncology practice is the poor services that we provide to our cancer survivors. Given the current state of knowledge, it is evident that what we do for survivor is small, fragmented and insufficient! And the service is more insufficient in patient who had been the more treated.
If one had surgery alone, the moral toll of losing a breast, burden of future relationship, perceived Disfiguration and related psychological detrimental effect is a tremendous burden to cope with...Consequences of true anatomic sequelae of surgeries are countless and a huge burden affecting the lives of survivors. And there are not enough trained psychologist or internists for that matter to meet the demand imposed by cancer on survivors.
If a survivor had Radiation, an additional toll occurs. Now on top of thyroid dysfunction, Xerostomia, chronic fatigue, and disfiguration, secondary cancer is added. Suppression of bone marrow after a localized radiation has always pointed out that although Radiation is localized, it has systemic implications. That is some altered protein escape the area to induce deleterious effects / stressful events at the distance. fatigue and sometimes nausea result from Radiation. Myocardial infarction, loss of hair and salivation are most of the time a result of a direct exposure to Radiation, and Anemia/Myelodysplasia can result from pelvic radiation.
And if chemotherapy was part of the treatment, and particularly if it contained Cisplatin or Alkylating agents, Leukemia and secondary cancers become a real possibility. Lung, renal and hearing toxicities become real. Chemotherapy induced encephalopaties of various level are present. Thyroid and fertility disturbances, Dysplasias or all kinds, and the overall neuro-psychiatric background is disturbed. Globally all senses are disturbed. Alterations of the immune system are poorly evaluated and understood.
Where we fail is in our correct evaluation of these disturbances and risk of future events in order to make a difference in the life of survivors. Our biomarkers are not up to what the should be for cancer early detection of secondary cancers,minor but significant side effcts are poorly measured and meaningful preventive or therapeutic measures are often lacking!
The point is that under the satisfaction of response to therapy, we fail to address what is to come for our survivors who often found themselves alone and unprepared to what is to come. The oncologist challenge is compounded by the fact that some of the services needed are not covered by insurers unless packaged in a certain smart fashion. Insurers who have paid for the treatment, want to run from the demanding patients! The lack of evidence based supportive treatment does not help either!
As to secondary cancers:
The point is that we know which cancers develop after chemotherapy
AML (CBF LIKE MOLECULE, GENETIC PROFILE OF BONE MARROW 1 YEAR POST TREATEMT?)
Myelodysplasia (genetic profile of Bone marrow
Colon Cancers( Microsattelite, MUC,
Lung cancers (HIF-1a, MUC...,EGFR)
Breast Cancers (WISP3,BRCA1,2...P53 mutation)
Lymphoma (appropriate gene translocations)
Sarcoma (WT-1, secretases)
and even Melanoma (p16,KIT,PTEN
But No one is delving into preventive detection of of genes!
Renal toxicity (NPHS2 gene, ACTN4
Ototoxicity same as renal (may be!)
scars (Metallopreoteases and their inhibition)
Many studies needed for "PROOF OF CONCEPT"
The skeptical will add "is this going to improve survival" just be in the shoes of survivors once and you will see the need for this testing!
It is quite apparant that one of the shame in Oncology practice is the poor services that we provide to our cancer survivors. Given the current state of knowledge, it is evident that what we do for survivor is small, fragmented and insufficient! And the service is more insufficient in patient who had been the more treated.
If one had surgery alone, the moral toll of losing a breast, burden of future relationship, perceived Disfiguration and related psychological detrimental effect is a tremendous burden to cope with...Consequences of true anatomic sequelae of surgeries are countless and a huge burden affecting the lives of survivors. And there are not enough trained psychologist or internists for that matter to meet the demand imposed by cancer on survivors.
If a survivor had Radiation, an additional toll occurs. Now on top of thyroid dysfunction, Xerostomia, chronic fatigue, and disfiguration, secondary cancer is added. Suppression of bone marrow after a localized radiation has always pointed out that although Radiation is localized, it has systemic implications. That is some altered protein escape the area to induce deleterious effects / stressful events at the distance. fatigue and sometimes nausea result from Radiation. Myocardial infarction, loss of hair and salivation are most of the time a result of a direct exposure to Radiation, and Anemia/Myelodysplasia can result from pelvic radiation.
And if chemotherapy was part of the treatment, and particularly if it contained Cisplatin or Alkylating agents, Leukemia and secondary cancers become a real possibility. Lung, renal and hearing toxicities become real. Chemotherapy induced encephalopaties of various level are present. Thyroid and fertility disturbances, Dysplasias or all kinds, and the overall neuro-psychiatric background is disturbed. Globally all senses are disturbed. Alterations of the immune system are poorly evaluated and understood.
Where we fail is in our correct evaluation of these disturbances and risk of future events in order to make a difference in the life of survivors. Our biomarkers are not up to what the should be for cancer early detection of secondary cancers,minor but significant side effcts are poorly measured and meaningful preventive or therapeutic measures are often lacking!
The point is that under the satisfaction of response to therapy, we fail to address what is to come for our survivors who often found themselves alone and unprepared to what is to come. The oncologist challenge is compounded by the fact that some of the services needed are not covered by insurers unless packaged in a certain smart fashion. Insurers who have paid for the treatment, want to run from the demanding patients! The lack of evidence based supportive treatment does not help either!
As to secondary cancers:
The point is that we know which cancers develop after chemotherapy
AML (CBF LIKE MOLECULE, GENETIC PROFILE OF BONE MARROW 1 YEAR POST TREATEMT?)
Myelodysplasia (genetic profile of Bone marrow
Colon Cancers( Microsattelite, MUC,
Lung cancers (HIF-1a, MUC...,EGFR)
Breast Cancers (WISP3,BRCA1,2...P53 mutation)
Lymphoma (appropriate gene translocations)
Sarcoma (WT-1, secretases)
and even Melanoma (p16,KIT,PTEN
But No one is delving into preventive detection of of genes!
Renal toxicity (NPHS2 gene, ACTN4
Ototoxicity same as renal (may be!)
scars (Metallopreoteases and their inhibition)
Many studies needed for "PROOF OF CONCEPT"
The skeptical will add "is this going to improve survival" just be in the shoes of survivors once and you will see the need for this testing!
Friday, August 2, 2013
MINIATURE BUSES TO DELIVER CHEMOTHERAPY WHERE WE WANT IT IN A CELL
"Research News: Breakthrough in Nano-Medicine Chemotherapy Drug Delivery in Phase II Trials"
NO KIDDING AROUND ANYMORE, ALL WE NEED TO KNOW IS A SPECIFIC ADDRESS IN A CELL AND THE BUS IS ON ITS WAY WITH WHATEVER THE CHEMOTHERAPY LOAD. THIS IS PRECISION MEDICINE/ONCOLOGY.
NANO PARTICLE TECHNOLOGY AT WORK FOR IMPROVED MEDICINE!
GO TO ARTICLE!
PUZZLING EXPERIENCE!
2 YEARS AGO I WAS SEEING A PATIENT WHO WAS FOUND WITH METASTATIC RENAL CANCER, I TALKED TO THE PATIENT ABOUT VARIOUS OPTIONS AT THE TIME
HIGH DOSE IL-2, THE MTOR INHIBITORS ETC...
SHE WAS AFRAID OF SIDE EFFECTS AND ASKED ME TO WAIT...
SHE CAME BACK 3 MONTHS LATER..FEARING PROGRESSION, I QUICKLY REQUESTED RADIOLOGIC EVALUATION
LESIONS WERE THE SAME...THIS CONVINCED ME AND THE PATIENT THAT ANOTHER 3
MONTHS OBSERVATION WAS REASONABLE....
3 MONTHS LATER ....SAME RESULTS
BY 9 MONTHS INTO THIS, I HAD TO ASK MY PATIENT TO CONFESS SINCE NOW I WAS IN DOUBT OF MY DIAGNOSIS:
SHE TOLD ME I AM TAKING "Echinacea"
"The immunomodulatory effects of echinacea preparations are likely caused by fat-soluble alkylamides (alkamides), which occur mostly in E. angustifolia and E. purpurea but not in E. pallida.[22] Alkylamides bind particularly to human CB2 and to a much lesser degree to CB1 cannabinoid receptors; as a result they are implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, cell migration and inhibition of tumor necrosis factor α TNF-alpha[23] These Alkylamides have similar potency to that of THC at the CB2 receptor, with THC being around 1.5 times stronger (~40 nm vs ~60 nm affinities). However, potency is dramatically less than that of THC at the psychoactive CB1 receptor (~40 nm vs ~ >1500 nm affinities).
As with any herbal preparation, individual doses may vary significantly in active chemical composition. In addition to poor process control which may affect inter- and intra-batch homogeneity, species, plant part, extraction method, and contamination or adulteration with other products all lead to variability between products.[24][25]"
Echinacea extracts inhibited growth of three species of trypanosomatids: Leishmania donovani, Leishmania major, and Trypanosoma brucei.[35]
========================================================================
Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits.[9][10] Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway,[9][10][11] a complex and highly conserved signal transduction pathway, which critically regulates a number of important cellular processes in both mature and developing tissues.[12] Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration[13] as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1).[11] The Zifi268 gene encodes a transcriptional regulator implicated in neuroplasticity and long term memory formation.[14]
At present, there are five recognized cannabinoids produced endogenously throughout the body: Arachidonoylethanolamine (anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine,[9] as well as the recently-discovered N-arachidonoyl-dopamine (NADA).[15] Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG preferentially activates the MAPK-ERK pathway, while noladin preferentially inhibits adenylyl cyclase.[9] Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB2 receptors.[9] Together, these results support the emerging concept of agonist-directed trafficking at the cannabinoid receptors." wikipedia
===============================
HIGH DOSE IL-2, THE MTOR INHIBITORS ETC...
SHE WAS AFRAID OF SIDE EFFECTS AND ASKED ME TO WAIT...
SHE CAME BACK 3 MONTHS LATER..FEARING PROGRESSION, I QUICKLY REQUESTED RADIOLOGIC EVALUATION
LESIONS WERE THE SAME...THIS CONVINCED ME AND THE PATIENT THAT ANOTHER 3
MONTHS OBSERVATION WAS REASONABLE....
3 MONTHS LATER ....SAME RESULTS
BY 9 MONTHS INTO THIS, I HAD TO ASK MY PATIENT TO CONFESS SINCE NOW I WAS IN DOUBT OF MY DIAGNOSIS:
SHE TOLD ME I AM TAKING "Echinacea"
TO THIS DAY I AM STILL PUZZLED!
They could be truth to this, it can be anti-opoptotic and anti-TNF.
Is it a lipoxin? because this LIPOXIN could do wonders in asthma!
THE CRBCM IS HARD AT WORK!
CAUTION:PROOF OF CONCEPT NEEDED!
Echinacea
from Wikipedia"The immunomodulatory effects of echinacea preparations are likely caused by fat-soluble alkylamides (alkamides), which occur mostly in E. angustifolia and E. purpurea but not in E. pallida.[22] Alkylamides bind particularly to human CB2 and to a much lesser degree to CB1 cannabinoid receptors; as a result they are implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, cell migration and inhibition of tumor necrosis factor α TNF-alpha[23] These Alkylamides have similar potency to that of THC at the CB2 receptor, with THC being around 1.5 times stronger (~40 nm vs ~60 nm affinities). However, potency is dramatically less than that of THC at the psychoactive CB1 receptor (~40 nm vs ~ >1500 nm affinities).
As with any herbal preparation, individual doses may vary significantly in active chemical composition. In addition to poor process control which may affect inter- and intra-batch homogeneity, species, plant part, extraction method, and contamination or adulteration with other products all lead to variability between products.[24][25]"
Echinacea extracts inhibited growth of three species of trypanosomatids: Leishmania donovani, Leishmania major, and Trypanosoma brucei.[35]
========================================================================
Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits.[9][10] Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway,[9][10][11] a complex and highly conserved signal transduction pathway, which critically regulates a number of important cellular processes in both mature and developing tissues.[12] Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration[13] as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1).[11] The Zifi268 gene encodes a transcriptional regulator implicated in neuroplasticity and long term memory formation.[14]
At present, there are five recognized cannabinoids produced endogenously throughout the body: Arachidonoylethanolamine (anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine,[9] as well as the recently-discovered N-arachidonoyl-dopamine (NADA).[15] Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG preferentially activates the MAPK-ERK pathway, while noladin preferentially inhibits adenylyl cyclase.[9] Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB2 receptors.[9] Together, these results support the emerging concept of agonist-directed trafficking at the cannabinoid receptors." wikipedia
===============================
Cancer prevention: A gobal failure of our current approach!
Our basic understanding of prevention is 2 fold or can be summarized in 2 main understanding scenarios
1: Stopping a continuous stimulation, or repression for that matter, of critical genes could prevent cancer:
- one suggests that the increasing rate of certain cancers can be justified by chronic stimulation of genes until an additional event happens to give an irreversible path to Neoplasia. This understanding is prominent among Oncologists and the public for that matter, but our reaction is rather confused or ineffective.
The insufficiency of response is mainly justified by our limitation of understanding of what follows the the prolong exposure or stimulation, which form of gene (heterogeneic type) is more susceptible and therefore requires early preventive measure, what gene actually triggers the neoplastic amplification, how long an exposure is critical for any specific individual, what other concurrent failure needs to be there to induce or help the neoplastic transformation (ie. mutation of CYP gene) and so on so forth...before these many questions, the human brain albeit scientific, has to stop. And our stopping to computer these events has worked for cancers to keep killing.
IT IS TIME TO USE MORE COMPUTER POWERS TO PREDICT NEOPLASTIC DEVELOPMENT TO ACTUALLY INTERVENE BASED ON COMPUTER MODELS THAT WE NEED TO CREATE RAPIDOS TO STOP CANCER DEVELOPMENT.
Once and for all, we need to stop reading this:
The incidence of liver cancer is rising worldwide and in the U.S. mostly due to the concomitant rise in hepatitis C viral infection. Because liver cancer occurs in the background of cirrhosis, preservation of healthy liver tissue is critically important. Liver cancer arising from the hepatocytes ....(johns Hopkins)
THIS STATEMENT ACKNOWLEDGES THE FACT THAT WE KNOW THE CAUSE OF THE INCREASE INCIDENCE OF LIVER CANCER BUT THERE IS NOT MUCH WE CAN DO TODAY DESPITE OUR ADVANCES. WE KNOW HEPATITIS C IS THE DRIVING FORCE BUT THERE LITTLE WE HAVE DONE SO FAR TO SQUARELY MEET THIS CHALLENGE. VACCINE ARE ONE WAY...BUT FOR HEPATITIS C IT IS NOT AVAILABLE!
"
A hepatitis C vaccine, a vaccine capable of protecting against hepatitis C, is not available. Although vaccines exist for hepatitis A and hepatitis B, development of a hepatitis C vaccine has presented challenges.[1] No vaccine is currently available, but several vaccines are currently under development.[2]
One effort has involved use of the hepatitis B core antigen.[3] In a 2006 study, 60 patients received four different doses of an experimental hepatitis C vaccine. All the patients produced antibodies that the researchers believe could protect them from the virus.[4] Nevertheless, as of 2008 vaccines are still being tested.[5][6] Some efforts have entered Phase I/II human clinical trials.[7]
SynCon will test a new HCV vaccine in humans in 2013. SyCon's HCV vaccine can generate robust T-cell responses not only in the blood, but also in the liver—an organ known to suppress T-cell activity."WIKIPEDIA....
For cancer of the Gatro-esophageal (GE) junction, we read:
"The possible reasons of the rise (in the incidence of this cancer) include the prevalence of obesity. elevated body mass index with increased incidence of GERD, and caloric consumption" the author even suggests "Use of Aspirin and other non steroidal anti-inflammatory agents has been associated with lower risk of cancers of the GE junction and other gastrointestinal tumors"(Grothey) YET THERE ARE NO NATIONAL COMPREHENSIVE PLAN TO USE THIS KNOWLEDGE.
REASON: Insufficient knowledge about what else these medications can cause, from bleeding to predisposing to arrhythmia in some of us on various medications. these fears block us from stopping these cancers.
IT IS TIME TO BRING IN THE POWER OF COMPUTER MODELS TO PLAN OUR APPROACHES!
(an exanple of gene suppression: CONTINUED SUPPRESSION OF PTEN! A PRECEDENT TO MANY DANGEROUS CANCERS! OR DECREASE OF E-CADHERIN...)
2. 2ND MAIN SCENARIO
IS USING FOOD SUPPLEMENT TO DAMPEN THESE STIMULATIONS OF GENE.
HERE THE ROLE ANTI-OXIDANTS IS CRITICAL.
WHAT I AM NOT SURE ABOUT IS WHETHER "FDA APPROVAL" STANDARD HAS HELPED OR DISCOURAGED PROGRESS IN THIS AREA...FURTHER PROOF OF CONCEPTS ARE NEEDED. THE SUGGESTION THAT STATUS OF IRON, ZINC, MAGNESIUM AND OTHER MINERALS CAN MODIFY THE EFFECTS OF ANTI-OXIDANTS HAS BEEN INSUFFICIENTLY STUDIED. SUSPICIONS ARE THAT WHAT IS GENERALLY GOOD AN INTERVENTION (TAKING VITAMINS, AND ANTI-OXIDANT FOOD STUFFS OR STAPLES, CAN BECOME DANGEROUS ! INDEED EVEN THE RATE OF CORRECTION OF IRON DEFICIENCY COULD BE DANGEROUS....DON'T GO TO FAST!) ONLY WELL DESIGNED COMPUTER MODELS CAN HELP US MANAGE ALL THESE PARAMETERS...AND WE ARE STILL NOWHERE NEAR THE GOAL!
WE NEED NEW BIOMARKERS FOR AUTOIMMUNE DISEASES...AGAIN COMPUTERS ARE NEEDED...WE CAN'T HANDLE THESE THINGS ON OUR OWN...THE EARLIER WE REALIZE THIS...THE BETTER!
CRBCM, WORKING ALWAYS!
1: Stopping a continuous stimulation, or repression for that matter, of critical genes could prevent cancer:
- one suggests that the increasing rate of certain cancers can be justified by chronic stimulation of genes until an additional event happens to give an irreversible path to Neoplasia. This understanding is prominent among Oncologists and the public for that matter, but our reaction is rather confused or ineffective.
The insufficiency of response is mainly justified by our limitation of understanding of what follows the the prolong exposure or stimulation, which form of gene (heterogeneic type) is more susceptible and therefore requires early preventive measure, what gene actually triggers the neoplastic amplification, how long an exposure is critical for any specific individual, what other concurrent failure needs to be there to induce or help the neoplastic transformation (ie. mutation of CYP gene) and so on so forth...before these many questions, the human brain albeit scientific, has to stop. And our stopping to computer these events has worked for cancers to keep killing.
IT IS TIME TO USE MORE COMPUTER POWERS TO PREDICT NEOPLASTIC DEVELOPMENT TO ACTUALLY INTERVENE BASED ON COMPUTER MODELS THAT WE NEED TO CREATE RAPIDOS TO STOP CANCER DEVELOPMENT.
Once and for all, we need to stop reading this:
The incidence of liver cancer is rising worldwide and in the U.S. mostly due to the concomitant rise in hepatitis C viral infection. Because liver cancer occurs in the background of cirrhosis, preservation of healthy liver tissue is critically important. Liver cancer arising from the hepatocytes ....(johns Hopkins)
THIS STATEMENT ACKNOWLEDGES THE FACT THAT WE KNOW THE CAUSE OF THE INCREASE INCIDENCE OF LIVER CANCER BUT THERE IS NOT MUCH WE CAN DO TODAY DESPITE OUR ADVANCES. WE KNOW HEPATITIS C IS THE DRIVING FORCE BUT THERE LITTLE WE HAVE DONE SO FAR TO SQUARELY MEET THIS CHALLENGE. VACCINE ARE ONE WAY...BUT FOR HEPATITIS C IT IS NOT AVAILABLE!
"
A hepatitis C vaccine, a vaccine capable of protecting against hepatitis C, is not available. Although vaccines exist for hepatitis A and hepatitis B, development of a hepatitis C vaccine has presented challenges.[1] No vaccine is currently available, but several vaccines are currently under development.[2]
One effort has involved use of the hepatitis B core antigen.[3] In a 2006 study, 60 patients received four different doses of an experimental hepatitis C vaccine. All the patients produced antibodies that the researchers believe could protect them from the virus.[4] Nevertheless, as of 2008 vaccines are still being tested.[5][6] Some efforts have entered Phase I/II human clinical trials.[7]
SynCon will test a new HCV vaccine in humans in 2013. SyCon's HCV vaccine can generate robust T-cell responses not only in the blood, but also in the liver—an organ known to suppress T-cell activity."WIKIPEDIA....
For cancer of the Gatro-esophageal (GE) junction, we read:
"The possible reasons of the rise (in the incidence of this cancer) include the prevalence of obesity. elevated body mass index with increased incidence of GERD, and caloric consumption" the author even suggests "Use of Aspirin and other non steroidal anti-inflammatory agents has been associated with lower risk of cancers of the GE junction and other gastrointestinal tumors"(Grothey) YET THERE ARE NO NATIONAL COMPREHENSIVE PLAN TO USE THIS KNOWLEDGE.
REASON: Insufficient knowledge about what else these medications can cause, from bleeding to predisposing to arrhythmia in some of us on various medications. these fears block us from stopping these cancers.
IT IS TIME TO BRING IN THE POWER OF COMPUTER MODELS TO PLAN OUR APPROACHES!
(an exanple of gene suppression: CONTINUED SUPPRESSION OF PTEN! A PRECEDENT TO MANY DANGEROUS CANCERS! OR DECREASE OF E-CADHERIN...)
2. 2ND MAIN SCENARIO
IS USING FOOD SUPPLEMENT TO DAMPEN THESE STIMULATIONS OF GENE.
HERE THE ROLE ANTI-OXIDANTS IS CRITICAL.
WHAT I AM NOT SURE ABOUT IS WHETHER "FDA APPROVAL" STANDARD HAS HELPED OR DISCOURAGED PROGRESS IN THIS AREA...FURTHER PROOF OF CONCEPTS ARE NEEDED. THE SUGGESTION THAT STATUS OF IRON, ZINC, MAGNESIUM AND OTHER MINERALS CAN MODIFY THE EFFECTS OF ANTI-OXIDANTS HAS BEEN INSUFFICIENTLY STUDIED. SUSPICIONS ARE THAT WHAT IS GENERALLY GOOD AN INTERVENTION (TAKING VITAMINS, AND ANTI-OXIDANT FOOD STUFFS OR STAPLES, CAN BECOME DANGEROUS ! INDEED EVEN THE RATE OF CORRECTION OF IRON DEFICIENCY COULD BE DANGEROUS....DON'T GO TO FAST!) ONLY WELL DESIGNED COMPUTER MODELS CAN HELP US MANAGE ALL THESE PARAMETERS...AND WE ARE STILL NOWHERE NEAR THE GOAL!
WE NEED NEW BIOMARKERS FOR AUTOIMMUNE DISEASES...AGAIN COMPUTERS ARE NEEDED...WE CAN'T HANDLE THESE THINGS ON OUR OWN...THE EARLIER WE REALIZE THIS...THE BETTER!
CRBCM, WORKING ALWAYS!
Thursday, August 1, 2013
GLAD TO FIND THE ANSWER TO THE SILENCE AT CPRIT
CPRIT Updates
Roadmap to Resuming Grant Awards
Since the legislature passed SB 149, CPRIT has been moving ahead with efforts to resume the agency’s grant awards process. View the CPRIT Roadmap to Resuming Grant Awards for a timeline and summary of activities and priorities critical for the agency to resume the grant awards process with deliberate purpose, accountability and transparency. As we continue to make progress, check back for updates on the status of individual activities and priorities.GO TO THE ROADMAP TO KNOW WHERE THEY ARE AT CPRIT!
Letter to the Texas Governor
RE: Citizen's Right to Petition that "No City Should be left Behind" by CPRIT.
As CPRIT is being restructured, The Coalition for the Reversal of Breast Cancer Mortality in African American Women (CRBCM), an IRS approved non profit Texan organization, and a responsible Citizen of this great state, would like to petition its Governor, influential Senators and the new Leaders at CPRIT to give El Paso finally a greater chance to participate in CPRIT's dream: Finding the cure for Cancer! We believe that until there is an overarching political will to meet the challenges of unfairness, disparity and gap in health care access, and the idea of the whole state of Texas, the participation in the CPRIT research funding program will remain fragmented and El Paso, once again, will be left behind.
Of the first almost one billion of dollars spent by CPRIT, less than one percent (1%) went to El Paso, the 6th City of Texas, population wise. The research community in El Paso has been left perplexed. There is a growing sense that this city is being "left behind" despite its size! It is not a contested fact that the major universities are located in the 3 major cities and have taken the lion share of CPRIT investments. We call, however, for a deliberate political regional intent and approach by the Texas Government in order to balance and promote development across all of Texas. We believe that a funded regional CPRIT office with focus on the WEST part of Texas will give us a better chance to participate in CPRIT efforts to reach the cure. While it is true that most El Paso institutions could not have matching funds to benefit from some CPRIT projects, it turns out that even some of the beneficiaries of CPRIT funding in other cities, eventually never proved the existence of the promised matching funds, and El Paso missed out on false pretenses as it turned out!
What we know for sure is that unless there is a political will to balance development in Texas and overcome the various disparities, the gap in development among cities will grow even more blatant! This is the reason for our petition! Even companies that were relocated to Texas as part of the CPRIT commercialization program, all flocked to Houston and Austin, (adding to the Houston traffic). None of significance stayed in El Paso! But El Paso is Texas, too! A rise of El Paso's share in CPRIT funding to 5% would be an impressive achievement and is not too much to ask for the 6th City in Texas!
We call your attention to this matter, NO CITY SHOULD BE LEFT BEHIND IN TEXAS, and your will can make a difference, a regional approach is called for.
Sincerely yours,
for the CRBCM, an El Paso institution
Dr Kankonde,
Oncologist and CEO
As CPRIT is being restructured, The Coalition for the Reversal of Breast Cancer Mortality in African American Women (CRBCM), an IRS approved non profit Texan organization, and a responsible Citizen of this great state, would like to petition its Governor, influential Senators and the new Leaders at CPRIT to give El Paso finally a greater chance to participate in CPRIT's dream: Finding the cure for Cancer! We believe that until there is an overarching political will to meet the challenges of unfairness, disparity and gap in health care access, and the idea of the whole state of Texas, the participation in the CPRIT research funding program will remain fragmented and El Paso, once again, will be left behind.
Of the first almost one billion of dollars spent by CPRIT, less than one percent (1%) went to El Paso, the 6th City of Texas, population wise. The research community in El Paso has been left perplexed. There is a growing sense that this city is being "left behind" despite its size! It is not a contested fact that the major universities are located in the 3 major cities and have taken the lion share of CPRIT investments. We call, however, for a deliberate political regional intent and approach by the Texas Government in order to balance and promote development across all of Texas. We believe that a funded regional CPRIT office with focus on the WEST part of Texas will give us a better chance to participate in CPRIT efforts to reach the cure. While it is true that most El Paso institutions could not have matching funds to benefit from some CPRIT projects, it turns out that even some of the beneficiaries of CPRIT funding in other cities, eventually never proved the existence of the promised matching funds, and El Paso missed out on false pretenses as it turned out!
What we know for sure is that unless there is a political will to balance development in Texas and overcome the various disparities, the gap in development among cities will grow even more blatant! This is the reason for our petition! Even companies that were relocated to Texas as part of the CPRIT commercialization program, all flocked to Houston and Austin, (adding to the Houston traffic). None of significance stayed in El Paso! But El Paso is Texas, too! A rise of El Paso's share in CPRIT funding to 5% would be an impressive achievement and is not too much to ask for the 6th City in Texas!
We call your attention to this matter, NO CITY SHOULD BE LEFT BEHIND IN TEXAS, and your will can make a difference, a regional approach is called for.
Sincerely yours,
for the CRBCM, an El Paso institution
Dr Kankonde,
Oncologist and CEO
IN RESPONSE TO VIEWERS'S QUESTIONS ABOUT CPRIT
Yes, CPRIT is going to resume operations soon!
We cannot tell when.
There has been complete silence from the Organization.
Activities and news about CPRIT have focused on the lack of actual oversight by the District Attorney Greg Abott who had appointed someone who missed a third of CPRIT critical meetings. DA Abott is now runing for the governorship in Texas!
CPRIT has 595 Millions in its coffers to give to mostly University projects. So we will hear sooner or later about this organization before the year ends. Based on its past performance, we expect that close to half of the money will go to 3 universities. We refuse to comment on the rest. There is no official news at CPRIT but you know the grapevine is still hard at work. We refuse to add to speculations. But we should mention that El Paso did not get its fair share the first time around with less than 1% of CPRIT grant attribution gone to the 4th City in Texas! And don't say we did not try to apply! CRBCM alone submitted 7 grant applications, none met somehow the political muscle requirements for funding! Now we are thinking we have a better chance with Deutche Krebshiffe, the Swiss Federal Government and Bundes Ministerium fur Bildung und Forschung than from CPRIT! In fact we got a UK funding for our genetic research being completed with UTEP help! The same project kindly declined by CPRIT!
How the new CPRIT will meet its expected many " raisons d'etre" is still to be seen. Abandoning its mission to Universities was the first achievement of the first dance...and we know what it led us to...let's wait and see the 2nd round...lets see how it meets the disparity challenge, and how it meets covering the whole Texas challenge...Remember all Taxpayers are coming together in this. The story of this organization will be talked about by historians for years to come! New leaders are being put into place, let's give them a chance to shine and amaze us! Take us to the cure of cancer!
We cannot tell when.
There has been complete silence from the Organization.
Activities and news about CPRIT have focused on the lack of actual oversight by the District Attorney Greg Abott who had appointed someone who missed a third of CPRIT critical meetings. DA Abott is now runing for the governorship in Texas!
CPRIT has 595 Millions in its coffers to give to mostly University projects. So we will hear sooner or later about this organization before the year ends. Based on its past performance, we expect that close to half of the money will go to 3 universities. We refuse to comment on the rest. There is no official news at CPRIT but you know the grapevine is still hard at work. We refuse to add to speculations. But we should mention that El Paso did not get its fair share the first time around with less than 1% of CPRIT grant attribution gone to the 4th City in Texas! And don't say we did not try to apply! CRBCM alone submitted 7 grant applications, none met somehow the political muscle requirements for funding! Now we are thinking we have a better chance with Deutche Krebshiffe, the Swiss Federal Government and Bundes Ministerium fur Bildung und Forschung than from CPRIT! In fact we got a UK funding for our genetic research being completed with UTEP help! The same project kindly declined by CPRIT!
How the new CPRIT will meet its expected many " raisons d'etre" is still to be seen. Abandoning its mission to Universities was the first achievement of the first dance...and we know what it led us to...let's wait and see the 2nd round...lets see how it meets the disparity challenge, and how it meets covering the whole Texas challenge...Remember all Taxpayers are coming together in this. The story of this organization will be talked about by historians for years to come! New leaders are being put into place, let's give them a chance to shine and amaze us! Take us to the cure of cancer!
Wednesday, July 31, 2013
ESTROGENIC RELATED EVENTS ARE STILL POORLY UNDERSTOOD!
In the life of of women, there is no event that has such profound implications than the onset of the reproductive phase! or the reign of Estrogen! Clearly, there are 3 phases to women's genetic life in our humble view:
Phase I life before Reproductive life
Phase II life during Reproductive life
Phase III life after Reproductive life
And in each phase, only Estrogen and related proteins make a difference by their absence or presence!
During phase I, the gene life is mostly influenced by the presence of the active X gene and "maturing" of all class of HLA genes as exposure to antigens of all kind occurs!
The rise of Estrogen in the second phase, deeply changes class I HLA expression to prepare the female body to receive a "foreign" body of an eventual infant! Many genes will be suppressed. And one of the ways they are suppressed is through hyper-Methylation. To this day, we do not have a sufficient description of the patterns of methylation that occur at this particular time! Understanding these epigenetic events has turned out to be critical Just one example that points to the importance of these events, are the high rates of complications with Lupus (and other autoimmune diseases) in women during this second phase. And remember, most congenital genetic based cancers express themselves during this period of time, that is why we suspect them to be genetic based (first clue in oncology practice)! i.e.Triple negative Breast cancer in a 30 Year old! Gives you the aha moment!
The retirement of Estrogen in the IIIrd phase induces so much cardiovascular havoc that books have been written about the devastations of menopause!
Describing patterns of epigenetic events in women in each phase is so critical and complicated we simply run away from it! But now, taking back courage, we are starting to look at it!
Phase I life before Reproductive life
Phase II life during Reproductive life
Phase III life after Reproductive life
And in each phase, only Estrogen and related proteins make a difference by their absence or presence!
During phase I, the gene life is mostly influenced by the presence of the active X gene and "maturing" of all class of HLA genes as exposure to antigens of all kind occurs!
The rise of Estrogen in the second phase, deeply changes class I HLA expression to prepare the female body to receive a "foreign" body of an eventual infant! Many genes will be suppressed. And one of the ways they are suppressed is through hyper-Methylation. To this day, we do not have a sufficient description of the patterns of methylation that occur at this particular time! Understanding these epigenetic events has turned out to be critical Just one example that points to the importance of these events, are the high rates of complications with Lupus (and other autoimmune diseases) in women during this second phase. And remember, most congenital genetic based cancers express themselves during this period of time, that is why we suspect them to be genetic based (first clue in oncology practice)! i.e.Triple negative Breast cancer in a 30 Year old! Gives you the aha moment!
The retirement of Estrogen in the IIIrd phase induces so much cardiovascular havoc that books have been written about the devastations of menopause!
Describing patterns of epigenetic events in women in each phase is so critical and complicated we simply run away from it! But now, taking back courage, we are starting to look at it!
IRON LEVEL MAY BE CRITICAL IN NON SMOKER LUNG CANCERS
Antioxidants may bring rage to the fire!
In communities which depend on Beta-carotene producing food staples ( " Foods rich in beta-carotene include orange fruits and vegetables such as apricots, cantaloupes, and carrots, as well as leafy green vegetables such as broccoli,spinach " etc..) and water supplies lacking iron, the combination of plenty antioxidants and iron deficiency could potentially be a problems particularly for women. Women in these regions are at increased risk of being Iron deficient because of Menses (Versus Men) and therefore could be at higher risk of developing "non smoker" type of lung cancers.
We are trying to look into this issue because a simple Iron monitoring of serum level of iron could reverse the the trend of lung cancer occurrence in these region. We should confess that Zinc level could have an impact as it goes hand in hand with Iron level as demonstrated in many studies.
Scientific basis of this suspicion
======================
"Recent studies have shed light on the mechanisms of hypoxia-driven stabilization of HIF-1α protein. Under normal oxygen tension, HIF-1α protein is hydroxylated on two proline residues by a family of oxygen-dependent prolyl hydroxylases (PHD1–3), and the modified HIF-1α becomes a substrate for polyubiquitination by a protein complex containing von Hippel-Lindau proteins (pVHL) and is thus targeted for degradation [1]. The enzymatic activities of PHD proteins are sensitive to oxygen availability. Under low-oxygen conditions, PHD proteins are unable to modify the HIF-1α protein, keeping HIF-1α protein unhydroxylated and allowing it to escape pVHL recognition and subsequent degradation, resulting in the triggering of the hypoxia responses [2]. HIF-1α protein is usually degraded under normal oxygen concentrations (normoxia), but in hypoxic conditions or in the presence of iron chelators, the degradation rate decreases, and HIF-1α protein accumulates and associates with HIF-1β to form a functional transcription complex, triggering the transcription of a host of hypoxia-inducible genes.
HIF-1α protein stabilization, however, is not limited to hypoxic conditions, and the so-called hypoxia responses can occur even with an adequate oxygen supply. This oxygen tension-independent hypoxia response can result from a wide range of possible genetic alterations and signaling malfunctions, including loss of VHL [3], p53 [4], or PTEN (a phosphatidylinositol trisphosphate lipid phosphatase) [5]; or activation of phosphatidylinositol 3-kinase/Akt [6] or Src pathways [7]. Hypoxia-independent HIF-1α protein stabilization is seen in patients with von Hippel-Lindau disease, a genetic disease in which one copy of the VHL gene is either inactivated or deleted. In these patients, when the remaining normal copy of the VHL gene is lost or inactivated, the HIF transcriptional complexes stay constitutively active, even under normal oxygen concentrations, due to faulty, pVHL-dependent degradation pathways. This dysregulated hypoxia pathway is a key factor in the development of multiple neoplasms in patients with von Hippel-Lindau disease [8]. CHI et al!"
You read correctly, in the "presence of iron Chelators" means iron deficiency.
And Iron deficiency is again worse in women who have menses ! The length of exposure to menses is increased in communities with "one child policy" since natural amenorrhea associated with child bearing is minimal in these society presumably. Rates of abortions may also play into the amount of iron deficiency in women in these regions. Length of the iron deficiency state and prolong exposure to antioxidants appear critical. So, iron deficiency will "protect" HIF-1 alpha protein from Ubiquitin dependent degradation and drive its association with HIF-1beta leading to stimulation or activation of transcription factors, MAPK pathways, and dangerous heterogeneic types of genes in the families of Rho, and Src. The direct involvement of the Estrogen cannot be discounted since Estrogen Receptors have been found activated in lung cancer tissue! Again give weight to the observation that it is indeed non smoker women are indeed the target of this disease.
FURTHER SUPPORTIVE EVIDENCES
======================
================================================
CLEARLY IT DOES NOT TAKE A GENIUS TO SEE THE POTENTIAL THREAD OF ASSOCIATION
Iron deficiency (and possibly Zinc amount or serum levels) could have a role. Remember Sirtuins and Butein uses in these regions are also increased. Src and related membrane located molecules have special sites of attachment for Iron. And level of iron affect deeply these molecule. The gene activator Erythropoietin is indeed here also!
one of the gene activated is VEGF which a complicated dance with EGFR. In some conditions, VEGF inhibits EGFR, in other it drive the activation of EGFR. And EGFR expression is peculiar in this disease, so much so that it would be illegal no to consider anti -EGFR as first line treatment in this disease!
=================================
NO MATTER THE STRENGTH OF THESE ASSERTIONS, PROOF OF CONCEPT IS NEEDED
REMEMBER A SIMPLE INTERVENTION COULD MAKE SO MUCH DIFFERENCE IN THE LIFE OF MANY!
SUPPORT RESEARCH AT CRBCM, CALL 915-307-3354 AND DONATE!
THE CRBCM IS A NON PROFIT ORGANIZATION RECOGNIZED BY THE IRS!
In communities which depend on Beta-carotene producing food staples ( " Foods rich in beta-carotene include orange fruits and vegetables such as apricots, cantaloupes, and carrots, as well as leafy green vegetables such as broccoli,spinach " etc..) and water supplies lacking iron, the combination of plenty antioxidants and iron deficiency could potentially be a problems particularly for women. Women in these regions are at increased risk of being Iron deficient because of Menses (Versus Men) and therefore could be at higher risk of developing "non smoker" type of lung cancers.
We are trying to look into this issue because a simple Iron monitoring of serum level of iron could reverse the the trend of lung cancer occurrence in these region. We should confess that Zinc level could have an impact as it goes hand in hand with Iron level as demonstrated in many studies.
Scientific basis of this suspicion
======================
"Recent studies have shed light on the mechanisms of hypoxia-driven stabilization of HIF-1α protein. Under normal oxygen tension, HIF-1α protein is hydroxylated on two proline residues by a family of oxygen-dependent prolyl hydroxylases (PHD1–3), and the modified HIF-1α becomes a substrate for polyubiquitination by a protein complex containing von Hippel-Lindau proteins (pVHL) and is thus targeted for degradation [1]. The enzymatic activities of PHD proteins are sensitive to oxygen availability. Under low-oxygen conditions, PHD proteins are unable to modify the HIF-1α protein, keeping HIF-1α protein unhydroxylated and allowing it to escape pVHL recognition and subsequent degradation, resulting in the triggering of the hypoxia responses [2]. HIF-1α protein is usually degraded under normal oxygen concentrations (normoxia), but in hypoxic conditions or in the presence of iron chelators, the degradation rate decreases, and HIF-1α protein accumulates and associates with HIF-1β to form a functional transcription complex, triggering the transcription of a host of hypoxia-inducible genes.
HIF-1α protein stabilization, however, is not limited to hypoxic conditions, and the so-called hypoxia responses can occur even with an adequate oxygen supply. This oxygen tension-independent hypoxia response can result from a wide range of possible genetic alterations and signaling malfunctions, including loss of VHL [3], p53 [4], or PTEN (a phosphatidylinositol trisphosphate lipid phosphatase) [5]; or activation of phosphatidylinositol 3-kinase/Akt [6] or Src pathways [7]. Hypoxia-independent HIF-1α protein stabilization is seen in patients with von Hippel-Lindau disease, a genetic disease in which one copy of the VHL gene is either inactivated or deleted. In these patients, when the remaining normal copy of the VHL gene is lost or inactivated, the HIF transcriptional complexes stay constitutively active, even under normal oxygen concentrations, due to faulty, pVHL-dependent degradation pathways. This dysregulated hypoxia pathway is a key factor in the development of multiple neoplasms in patients with von Hippel-Lindau disease [8]. CHI et al!"
You read correctly, in the "presence of iron Chelators" means iron deficiency.
And Iron deficiency is again worse in women who have menses ! The length of exposure to menses is increased in communities with "one child policy" since natural amenorrhea associated with child bearing is minimal in these society presumably. Rates of abortions may also play into the amount of iron deficiency in women in these regions. Length of the iron deficiency state and prolong exposure to antioxidants appear critical. So, iron deficiency will "protect" HIF-1 alpha protein from Ubiquitin dependent degradation and drive its association with HIF-1beta leading to stimulation or activation of transcription factors, MAPK pathways, and dangerous heterogeneic types of genes in the families of Rho, and Src. The direct involvement of the Estrogen cannot be discounted since Estrogen Receptors have been found activated in lung cancer tissue! Again give weight to the observation that it is indeed non smoker women are indeed the target of this disease.
FURTHER SUPPORTIVE EVIDENCES
======================
The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents.
Source
Medical Oncology Service, Vall d'Hebron University Hospital, P. Vall d'Hebron, 119-129, 08035 Barcelona, Spain. jtabernero@vhebron.netAbstract
Multiple
cellular pathways influence the growth and metastatic potential of
tumors. This creates heterogeneity, redundancy, and the potential for
tumors to bypass signaling pathway blockade, resulting in primary or
acquired resistance. Combining therapies that inhibit different
signaling pathways has the potential to be more effective than
inhibition of a single pathway and to overcome tumor resistance.
Vascular endothelial growth factor (VEGF) and epidermal growth factor
receptor (EGFR) inhibitors have become key therapies in several tumor
types. Close relationships between these factors exist: VEGF signaling
is up-regulated by EGFR expression and, conversely, VEGF up-regulation
independent of EGFR signaling seems to contribute to resistance to EGFR
inhibition. Therefore, inhibition of both pathways could improve
antitumor efficacy and overcome resistance to EGFR inhibition.
Preclinical studies have shown that VEGF and EGFR inhibitors can have
additive effects and that combined inhibition is effective in EGFR
inhibitor-resistant cell lines. Clinical trials have also produced
promising data: combining the anti-VEGF monoclonal antibody bevacizumab
with the anti-EGFR antibody cetuximab or the EGFR tyrosine kinase
inhibitor erlotinib increases benefit compared with either of these
anti-EGFR agents alone or combined with chemotherapy. The potential of
this novel approach to anticancer therapy will be elucidated by large,
ongoing clinical trials.
. No significant differences existed between treated patients at 6 wk and at the end of the study. The erythrocyte levels of catalase, SOD, and GSH-Px were significantly lower in treated patients relative to controls (p<0.05). These levels increased after 6 wk of supplementation (p<0.05) and showed no significant differences with those at the end of the study.
Effect of iron supplementation on oxidative stress and antioxidant status in iron-deficiency anemia.
Source
Department of Hematology, Medical School, Selcuk University, Konya, Turkey.Abstract
The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents.
Source
Medical Oncology Service, Vall d'Hebron University Hospital, P. Vall d'Hebron, 119-129, 08035 Barcelona, Spain. jtabernero@vhebron.netAbstract
Multiple cellular pathways influence the growth and metastatic potential of tumors. This creates heterogeneity, redundancy, and the potential for tumors to bypass signaling pathway blockade, resulting in primary or acquired resistance. Combining therapies that inhibit different signaling pathways has the potential to be more effective than inhibition of a single pathway and to overcome tumor resistance. Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors have become key therapies in several tumor types. Close relationships between these factors exist: VEGF signaling is up-regulated by EGFR expression and, conversely, VEGF up-regulation independent of EGFR signaling seems to contribute to resistance to EGFR inhibition. Therefore, inhibition of both pathways could improve antitumor efficacy and overcome resistance to EGFR inhibition. Preclinical studies have shown that VEGF and EGFR inhibitors can have additive effects and that combined inhibition is effective in EGFR inhibitor-resistant cell lines. Clinical trials have also produced promising data: combining the anti-VEGF monoclonal antibody bevacizumab with the anti-EGFR antibody cetuximab or the EGFR tyrosine kinase inhibitor erlotinib increases benefit compared with either of these anti-EGFR agents alone or combined with chemotherapy. The potential of this novel approach to anticancer therapy will be elucidated by large, ongoing clinical trials.. No significant differences existed between treated patients at 6 wk and at the end of the study. The erythrocyte levels of catalase, SOD, and GSH-Px were significantly lower in treated patients relative to controls (p<0.05). These levels increased after 6 wk of supplementation (p<0.05) and showed no significant differences with those at the end of the study.
AND WE THANK RESEARCHERS QUOTED HERE FOR THEIR CONTRIBUTIONS!
================================================
CLEARLY IT DOES NOT TAKE A GENIUS TO SEE THE POTENTIAL THREAD OF ASSOCIATION
Iron deficiency (and possibly Zinc amount or serum levels) could have a role. Remember Sirtuins and Butein uses in these regions are also increased. Src and related membrane located molecules have special sites of attachment for Iron. And level of iron affect deeply these molecule. The gene activator Erythropoietin is indeed here also!
one of the gene activated is VEGF which a complicated dance with EGFR. In some conditions, VEGF inhibits EGFR, in other it drive the activation of EGFR. And EGFR expression is peculiar in this disease, so much so that it would be illegal no to consider anti -EGFR as first line treatment in this disease!
=================================
NO MATTER THE STRENGTH OF THESE ASSERTIONS, PROOF OF CONCEPT IS NEEDED
REMEMBER A SIMPLE INTERVENTION COULD MAKE SO MUCH DIFFERENCE IN THE LIFE OF MANY!
SUPPORT RESEARCH AT CRBCM, CALL 915-307-3354 AND DONATE!
THE CRBCM IS A NON PROFIT ORGANIZATION RECOGNIZED BY THE IRS!
CAN YOU BEAT 100% IN LYMPHOMA MANAGEMENT?
| Ibrutinib/R-CHOP Combination Achieves 100% Response Rate in Non-Hodgkin Lymphoma | ||
| Read more >> | ||
| Ganetespib-Docetaxel Combination Improves Survival in GALAXY-1 Trial | ||
| Read more >> | ||
| Proteins Identified as Potential Biomarkers for Response in KRAS-Mutated NSCLC go to targeted healthcare communications for more! targetedHC. |
STRONG PROPOSED COLLABORATION WITH THE UNIVERSITY OF TEXAS AT EL PASO (UTEP).
PROGRESS AT CRBCM
===================================================
With the University lending its hands and laboratory support, the CRBCM has entered the serious phase of research production. We will embark on a lung cancer project which was funded partially by MDHonors as previously disclosed.
The laboratory support work will be completed by
.DR CHAI YURONG, a visiting scholar from ZHENGZHOU UNIVERSITY IN CHINA.
The CRBCM family would like to take this opportunity to congratulate publicly Professor Jiang Zhang who was made FULL PROFESSOR this month at UTEP. We thank him for his work!
The CRBCM, working with only the best!
OF NOTE, WE THANK THE EL PASO DEPARTMENT OF HEALTH FOR RECOMMENDING US TO PROFESSOR ZHANG!
Dear Dr. Kankonde,
It was nice meeting with you and Peggy!
Please see the attached proposal draft. If you have any comments or suggestions, please let me know.
Best regards,
Jianying Zhang,
M.D., Ph.D.
Associate Professor
Department of Biological Sciences
The University of Texas at El Paso
500 West University Avenue
El Paso, Texas 79968
Tel: 915-747-6995 (office); 915-747-5343/5183 (lab)===================================================
With the University lending its hands and laboratory support, the CRBCM has entered the serious phase of research production. We will embark on a lung cancer project which was funded partially by MDHonors as previously disclosed.
The laboratory support work will be completed by
.DR CHAI YURONG, a visiting scholar from ZHENGZHOU UNIVERSITY IN CHINA.
The CRBCM family would like to take this opportunity to congratulate publicly Professor Jiang Zhang who was made FULL PROFESSOR this month at UTEP. We thank him for his work!
The CRBCM, working with only the best!
OF NOTE, WE THANK THE EL PASO DEPARTMENT OF HEALTH FOR RECOMMENDING US TO PROFESSOR ZHANG!
Monday, July 29, 2013
CRBCM at the Health Fair of Foundation Surgical Hospital in El Paso
Recruiting volunteers for the National Cancer 3 Study aged between 30 and 65 who have not had a diagnosis of cancer: We are knocking out cancer !
The response was tremendous, the majority of the visitors of the CRBCM's booth took the pledge to participate in the study and to help better understand and better fight cancer, and to finally help put EL PASO back on the map of Cancer research and request funding in proportion of the population and its real and yet chronically unmet needs which are huge!
The response was tremendous, the majority of the visitors of the CRBCM's booth took the pledge to participate in the study and to help better understand and better fight cancer, and to finally help put EL PASO back on the map of Cancer research and request funding in proportion of the population and its real and yet chronically unmet needs which are huge!
BREAKING THROUGH: ANTIOXIDANTS MAY BE DANGEROUS IN A SETTING OF IRON DEFICIENCY: THE LUNG CANCER STORY
AT ISSUE: LUNG CANCER IN NON SMOKER, PROMINENT IN WOMEN
According to Lynne Eldridge MD
"Overall, 10-15% of lung cancers occur in non-smokers. (Another 50% occur in former smokers.)
Two-thirds of the non-smokers who get lung cancer are women, and 20% of lung cancers in women occur in individuals who have never smoked. This percentage is significantly higher in Asian women."
--------------------------------
Now, the inferences to this statement are:
1. That there is something peculiar in women, particularly of Asian origin, that predispose them to this Cancer. And what we know about women in general is that they have more Estrogen than men. And that, in general women tend to be more Iron deficient because of their Menses! The one child policy increases Estrogen fluctuation exposure and prolonged menses period, and therefore the likelihood of iron deficiency!
2. Asian women are known for their good diet full of Anti-oxidants (Nuts, Green tea, etc.), and their Beta-carotene based nutrition (Pumpkins, carots, apricots ) exposing them to increased amounts of Vitamin A.
3. "10-15% of lung cancers in non smokers" means in the United States alone where there will be 222,520 new cases, we are talking about 30,000 new cases of lung cancers in non smokers who are somewhat involved by this hypothetical discussion.
4. WHO: "recent studies have shown that the intakes of Calcium Zinc Magnesium, Potassium and other essential minerals were insufficient and are a traditional problem in the chinese diet" Chen J Gao et al.
This implicates Zinc deficiency which has documented interactions with Iron. This implicates the water supply as a poor source of Iron or Zinc for that matter. WHO has not proposed any guideline values for Iron in drinking water. "The average iron value in water supplies across Hong Kong is very low (2.2 millions families are affected by this deficiency"(Fox Yi hu)
5. "Beta-carotene supplementation was associated with an increased risk of lung cancer among high risk populations of heavy smokers in 2 out of 3 clinical trials" (David Gerber et al!)
THERE WAS NO OBSERVATION LOOKING AT THE SERUM LEVEL OF IRON OR ZINC IN THE EVALUATION OF THIS RISK!
According to Lynne Eldridge MD
"Overall, 10-15% of lung cancers occur in non-smokers. (Another 50% occur in former smokers.)
Two-thirds of the non-smokers who get lung cancer are women, and 20% of lung cancers in women occur in individuals who have never smoked. This percentage is significantly higher in Asian women."
--------------------------------
Now, the inferences to this statement are:
1. That there is something peculiar in women, particularly of Asian origin, that predispose them to this Cancer. And what we know about women in general is that they have more Estrogen than men. And that, in general women tend to be more Iron deficient because of their Menses! The one child policy increases Estrogen fluctuation exposure and prolonged menses period, and therefore the likelihood of iron deficiency!
2. Asian women are known for their good diet full of Anti-oxidants (Nuts, Green tea, etc.), and their Beta-carotene based nutrition (Pumpkins, carots, apricots ) exposing them to increased amounts of Vitamin A.
3. "10-15% of lung cancers in non smokers" means in the United States alone where there will be 222,520 new cases, we are talking about 30,000 new cases of lung cancers in non smokers who are somewhat involved by this hypothetical discussion.
4. WHO: "recent studies have shown that the intakes of Calcium Zinc Magnesium, Potassium and other essential minerals were insufficient and are a traditional problem in the chinese diet" Chen J Gao et al.
This implicates Zinc deficiency which has documented interactions with Iron. This implicates the water supply as a poor source of Iron or Zinc for that matter. WHO has not proposed any guideline values for Iron in drinking water. "The average iron value in water supplies across Hong Kong is very low (2.2 millions families are affected by this deficiency"(Fox Yi hu)
5. "Beta-carotene supplementation was associated with an increased risk of lung cancer among high risk populations of heavy smokers in 2 out of 3 clinical trials" (David Gerber et al!)
THERE WAS NO OBSERVATION LOOKING AT THE SERUM LEVEL OF IRON OR ZINC IN THE EVALUATION OF THIS RISK!
Saturday, July 27, 2013
ACTIVITY AT THE CRBCM
Good Morning every one, we have completed 2 weeks of work in Fort Wayne IN conducting field work. Very successful Mission which keeps the CRBCM funded for future endeavors! We are returning to El Paso for a very active work load. From Covering Local Hospitals to participating to Community Activity at Physician Hospital of El Paso. (We will put up some Pics when they become available).
This week we will meet again with UTEP staff in order to further reaffirm details of our collaboration on our specific Research program. The CRBCM will also visit one of the 4 Grifols' Plasma Centers. Work at the Greater East cancer Center also awaits attention.
The CRBCM has been working on several projects which need finalization.
Attending an important Oncology Conference in Miami will help obtain further questions to be explored in our blog. Contractual agreements limit some disclosures.
Keeping busy, legal and efficient will be the focus at CRBM.
This week we will meet again with UTEP staff in order to further reaffirm details of our collaboration on our specific Research program. The CRBCM will also visit one of the 4 Grifols' Plasma Centers. Work at the Greater East cancer Center also awaits attention.
The CRBCM has been working on several projects which need finalization.
Attending an important Oncology Conference in Miami will help obtain further questions to be explored in our blog. Contractual agreements limit some disclosures.
Keeping busy, legal and efficient will be the focus at CRBM.
Friday, July 26, 2013
EPIGENETIC PHENOMENA ARE CRITICAL IN GENE EXPRESSION...
It is now clear that the DNA expression is clearly an important parameter in the destiny of the cell, be it normal or cancerous, the cell destiny is determined by its potential forces built in its DNA. But as the cell live, there are phenotypic influences imposed by postranslational modifications brought on by epigenetic events which ultimately shape further DNA expression.
These events have been described by others
and include:
1.Histones Modification
2.DNA Methylation or lack of!(Hypomethylation)
3."Nucleosome positioning"
4,Activity of MicroRNA
5.Gene to Gene suppression of expression
we will discuss each as it is pertinent.
But please don't believe that this all. Indeed:
1.Abnormal Splicing (Frame shift)
2.Point Mutations
3.Disabling of DNA repair
4.Gene cross-talking
5.Enzyme deficiency and
6. Alteration of Homeobox Molecule and arrangements therein ...
WILL ALL AFFECT DNA EXPRESSION AND POTENTIALLY BE A DRIVING FORCE TO ABNORMALITY IN THE CELL!
It is now clear that the DNA expression is clearly an important parameter in the destiny of the cell, be it normal or cancerous, the cell destiny is determined by its potential forces built in its DNA. But as the cell live, there are phenotypic influences imposed by postranslational modifications brought on by epigenetic events which ultimately shape further DNA expression.
These events have been described by others
and include:
1.Histones Modification
2.DNA Methylation or lack of!(Hypomethylation)
3."Nucleosome positioning"
4,Activity of MicroRNA
5.Gene to Gene suppression of expression
we will discuss each as it is pertinent.
But please don't believe that this all. Indeed:
1.Abnormal Splicing (Frame shift)
2.Point Mutations
3.Disabling of DNA repair
4.Gene cross-talking
5.Enzyme deficiency and
6. Alteration of Homeobox Molecule and arrangements therein ...
WILL ALL AFFECT DNA EXPRESSION AND POTENTIALLY BE A DRIVING FORCE TO ABNORMALITY IN THE CELL!
With lack of signs of life at CPRIT,
the Burnt Orange report is news! and juicy (I meant spicy!)
(Thanks to the Lone Star Project for helping to shine a light on the connections between Abbott and CPRIT. - promoted by Katherine Haenschen)
(Originally posted at the Lone Star Project)
For voters, it seemed to make sense for the State Attorney General, our
top civil law enforcement official, to sit on the board of the newly
created Cancer Research Institute of Texas (CPRIT). The promise of new
and innovative treatments for cancer was clearly a worthwhile state
expenditure, but accountability would be needed. With millions of tax
dollars flowing through the agency to private companies, a State
official with law enforcement responsibilities diligently conducting
oversight would deter improper activity and, if improprieties occurred,
could move quickly to investigate and prosecute.
So much for reasonable expectations. It turns out that Texas AG Greg Abbott sitting on the oversight board was a green light rather than a caution sign to many of these key donors. Businesses backed by Abbott contributors - many of whom are partisan Republicans - have received large grants and contracts from CPRIT without fear of any oversight at all.
(
Read more below the jump. (please go to the full damaging report)
====================YOU CANNOT LEAD FROM BEHIND! YOU CAN NOT CONTROL WHAT IS SAID BY HIDING! MEET THE CHALLENGE RIGHT IN FRONT!
the Burnt Orange report is news! and juicy (I meant spicy!)
Greg Abbott, CPRIT, And Favors for Friends
by: Lone Star Project
Mon Jul 22, 2013 at 07:17 PM CDT
(Thanks to the Lone Star Project for helping to shine a light on the connections between Abbott and CPRIT. - promoted by Katherine Haenschen)
(Originally posted at the Lone Star Project)
For voters, it seemed to make sense for the State Attorney General, our
top civil law enforcement official, to sit on the board of the newly
created Cancer Research Institute of Texas (CPRIT). The promise of new
and innovative treatments for cancer was clearly a worthwhile state
expenditure, but accountability would be needed. With millions of tax
dollars flowing through the agency to private companies, a State
official with law enforcement responsibilities diligently conducting
oversight would deter improper activity and, if improprieties occurred,
could move quickly to investigate and prosecute.So much for reasonable expectations. It turns out that Texas AG Greg Abbott sitting on the oversight board was a green light rather than a caution sign to many of these key donors. Businesses backed by Abbott contributors - many of whom are partisan Republicans - have received large grants and contracts from CPRIT without fear of any oversight at all.
(
Read more below the jump. (please go to the full damaging report)
====================YOU CANNOT LEAD FROM BEHIND! YOU CAN NOT CONTROL WHAT IS SAID BY HIDING! MEET THE CHALLENGE RIGHT IN FRONT!
Thursday, July 25, 2013
AS OF JULY 25TH, 2013/ VISITORS AT CRBCM
|
AS OF JULY 25TH 2013
| Entry | Pageviews |
|---|---|
United States
|
14874
|
Russia
|
1882
|
Germany
|
1120
|
France
|
417
|
United Kingdom
|
385
|
Ukraine
|
278
|
Poland
|
244
|
China
|
144
|
Sweden
|
92
|
Taiwan
|
80
|
NEW TARGET THERAPY AT THE HORIZON
When a cell becomes cancerous, one of the thing to ensure survival is to multiply and move away from the original site to find food and ensure to escape immune surveillance. Indeed a localized cell will end-up being reported as it changes its receptors and membrane proteins. Its neighbors will tell on it as it will escape the consensus required and set in place by the NOTCH. But a normal cell is well specialized in order to participate to the Notch controlled function of the tissue to which it belongs. A cell in the liver, will be differentiated to do liver function. and the more a cell differentiate, the less it can multiply. For the cell that is now cancerous, one of the way to recuperate its multiplication potential is to de-differentiate, lose the differentiation, becoming more totipotential. It is known that forcing leukemic cell for example into full differentiation, will control the disease.
The finding that an epigenetic phenomena can return totipotentiality to the cell marks a significant discovery
XU et al :" that expression of microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells (hESCs) but highly upregulated during differentiation. We identify the pluripotency factors OCT4, SOX2, and KLF4 as direct targets of miR-145 and show that endogenous miR-145 represses the 3' untranslated regions of OCT4, SOX2, and KLF4." "Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells,"LIU ET AL
This means cancer cell have to suppress mi-145 to recoup self renewal...this is a powerful pathways that need to be absolutely tampered with particularly in hematologic malignancies!
GET BACK TO WORK WITH THE CRBCM! PROOF OF CONCEPT NEEDED!
The finding that an epigenetic phenomena can return totipotentiality to the cell marks a significant discovery
XU et al :" that expression of microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells (hESCs) but highly upregulated during differentiation. We identify the pluripotency factors OCT4, SOX2, and KLF4 as direct targets of miR-145 and show that endogenous miR-145 represses the 3' untranslated regions of OCT4, SOX2, and KLF4." "Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells,"LIU ET AL
This means cancer cell have to suppress mi-145 to recoup self renewal...this is a powerful pathways that need to be absolutely tampered with particularly in hematologic malignancies!
GET BACK TO WORK WITH THE CRBCM! PROOF OF CONCEPT NEEDED!
The CRBCM is proud to announce that work funded BY MDHonors is taking shape. Our consultation and collaborative setting with UTEP is in place. The CRBCM is encouraged by the mighty help it will get from DR Prof Zhang on this work. We thank also the University of Virginia Tissue Bank for all its help. Work is before us. Let's go for it!
|  12:54 PM (5 hours ago) | | ||
| ||||
Jul25Thu
|
Lung Cancer Research w/ Dr. Zhang
Yes
Maybe
No
|
When: Thursday, July 25, 2013 3:30 PM-4:30 PM (UTC-07:00) Mountain Time (US & Canada).
Where: Dr. Oseguedas Office
Note: The GMT offset above does not reflect daylight saving time adjustments.
*~*~*~*~*~*~*~*~*~*
Dear All,
Dr. Osegueda and Dr. Zhang will be meeting with Peggy today.
Dr. Aguilera, they will be meeting without you today.
Thank you,
Ana
=================================
A FOLLOW-UP MEETING IS SCHEDULED FOR THIS COMING TUESDAY
THE CRBCM IS UPBEAT, WE ARE IN PLAY...
THERE IS A BUZZ OF EXCITEMENT
DOORS ARE OPENING
The Notch once again!
"Migraine with Aura often precede the strokes by several years.The responsible gene on chromosome 19 results in Mutations of the Notch3 Receptor protein."...(Zivin)
DON'T FIX IT IF IT IS NOT BROKEN
An 84 year man saw on TV an advertising about a new molecule in the nutritional supplement (not FDA approved). The molecule was said to "bust" blood clot and unclog circulation. He figured that this new medicine must be better then Aspirin he was taking for clotting prevention. He stopped Aspirin, and while waiting for the new drug, he developed a stroke. The new medication failed to reverse the stroke induce hemiplegia....lesson to learn from...better prevent things, and keep on doing what works!
DON'T FIX IT IF IT IS NOT BROKEN
An 84 year man saw on TV an advertising about a new molecule in the nutritional supplement (not FDA approved). The molecule was said to "bust" blood clot and unclog circulation. He figured that this new medicine must be better then Aspirin he was taking for clotting prevention. He stopped Aspirin, and while waiting for the new drug, he developed a stroke. The new medication failed to reverse the stroke induce hemiplegia....lesson to learn from...better prevent things, and keep on doing what works!
Wednesday, July 24, 2013
CRBCM, moving mountains
We were right not to give up. We seem to have a match. The University of Texas at El Paso seems to have finally responded...It appears they will work with us on the Research project. Now watch our enemies go to work to stop progress. The CRBCM is advancing ever since we understood we can not lead from behind! We have found the right match, progress is with us, on our side.
Still in Fort Wayne Indianna for another CRBCM contract, will be back in El Paso this week-end. Then will prepare a trip for Miami...The CRBCM, Advancing in the face of adversity but building collaboration all the way...CRBCM, an engine of progress toward the cure ... We submitted new conceptual research projects for review today...breaking new ways in a path of stone...
Still in Fort Wayne Indianna for another CRBCM contract, will be back in El Paso this week-end. Then will prepare a trip for Miami...The CRBCM, Advancing in the face of adversity but building collaboration all the way...CRBCM, an engine of progress toward the cure ... We submitted new conceptual research projects for review today...breaking new ways in a path of stone...
FORCES AGAINST PROGRESS TO THE CURE
We continue to maintain that political forces are the best ally to cancer,
to search for and reach the cure, one needs support, financial resources, and political muscles. And none of these involve the actual research that will be needed to reach the cure. The CRBCM was close to obtaining the PCR machine that would have put us as an independent contender in the race for the cure of cancer. But political forces worked in the dark to stop the acquisition. Indeed we did not know that the who's who we were dealing with WERE CONNECTED TO OUR COMPETITORS...suffice is to say that phone calls and meetings in the dark of the night occurred and the plug has been pulled on this acquisition...the CRBCM has lived another setback in this political world and our intended research received another setback...cancer in the meanwhile is still killing...but we are a Coalition and the fight continues...
After a fall, stand up to fight yet another day...people would rather keep a valuable instrument (PCR machine) bought with public money in a closet unused rather than lending it to CRBCM. In the closet, with no use, it is rotting and soon will become obsolete... but that what happen in a small world full of politics!
The CRBCM meanwhile continues its road because we believe our cause is just...and we will not fail in our commitment to realize our mission. The CRBCM is a mission driven company...will continue our path until our enemies become irrelevant...
to search for and reach the cure, one needs support, financial resources, and political muscles. And none of these involve the actual research that will be needed to reach the cure. The CRBCM was close to obtaining the PCR machine that would have put us as an independent contender in the race for the cure of cancer. But political forces worked in the dark to stop the acquisition. Indeed we did not know that the who's who we were dealing with WERE CONNECTED TO OUR COMPETITORS...suffice is to say that phone calls and meetings in the dark of the night occurred and the plug has been pulled on this acquisition...the CRBCM has lived another setback in this political world and our intended research received another setback...cancer in the meanwhile is still killing...but we are a Coalition and the fight continues...
After a fall, stand up to fight yet another day...people would rather keep a valuable instrument (PCR machine) bought with public money in a closet unused rather than lending it to CRBCM. In the closet, with no use, it is rotting and soon will become obsolete... but that what happen in a small world full of politics!
The CRBCM meanwhile continues its road because we believe our cause is just...and we will not fail in our commitment to realize our mission. The CRBCM is a mission driven company...will continue our path until our enemies become irrelevant...
Monday, July 22, 2013
PROGRESS IN TARGETING THERAPY IN UVEAL MELANOMA
ADDING INTERFERON WOULD MAKE MORE SENSE THAN ADDING AVASTIN TO SIROLIMUS IN UVEAL MELANOMA.
Uveal Melanoma has been now extensively studied and has been associated in up to 50% of cases, to GNAQ/GNA11 genes, these is basically a G-protein, a switch that stays on in patient amplifying permanently the MAPK pathways, and therefore the MTOR. This fact amplifies the role of MTOR inhibitors in this disease's treatment.
Although Avastin could have a role by involving another target, it seems that intervening at epigenic level by using Dasatinib or by using a known effective agent such as interferon would add more. The caveat here is that epigenic intervention could tamper with MTOR expression proper and Mitigate the role of its inhibitor. Suffice is to say that intervention at epigenic level could prove additive to MTOR inhibitors. It is still to be established whether purified Hamartin, a derivative from TCS1 gene (in combination or not with Tuberin-TSC2) may prove synergestic to MTOR inhibitors...
Uveal Melanoma has been now extensively studied and has been associated in up to 50% of cases, to GNAQ/GNA11 genes, these is basically a G-protein, a switch that stays on in patient amplifying permanently the MAPK pathways, and therefore the MTOR. This fact amplifies the role of MTOR inhibitors in this disease's treatment.
Although Avastin could have a role by involving another target, it seems that intervening at epigenic level by using Dasatinib or by using a known effective agent such as interferon would add more. The caveat here is that epigenic intervention could tamper with MTOR expression proper and Mitigate the role of its inhibitor. Suffice is to say that intervention at epigenic level could prove additive to MTOR inhibitors. It is still to be established whether purified Hamartin, a derivative from TCS1 gene (in combination or not with Tuberin-TSC2) may prove synergestic to MTOR inhibitors...
Saturday, July 20, 2013
Transplant
Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. It is a medical procedure in the fields of hematology and oncology, most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia.
In these cases, the recipient's immune system is usually destroyed with
radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease is a major complication of allogenic HSCT.
Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As the survival of the procedure increases, its use has expanded beyond cancer, such as autoimmune diseases.[1][2] wikipedia
==================================================================
Around the World over 50,000 Bone marrow transplants occur now each year. Bringing cure to many lives. When it is allogeneic, the graft-versus tumor effect prolongs the cancer killing...yielding better cure rates, sometime at the risk of graft versus host disease that requires careful management. In most leukemia, Allogeneic transplant is the only curative option (CML). Transplant can also restore immuno-deficiency in congenital syndromes such as the Wiskott-Aldrich Syndrome and the severe combined deficiency-immunodeficiency syndrome.
When the risk is reasonable, transplant has been indicated to:
1.Restore defectuous Red Blood Cells (Aplastic Anemias, Thalassemias,
2.Restore deficient enzymatic and metabolic diseases (Gaucher disease)
3.fight malignancies by allowing to use high doses of both Radiation and chemotherapy when Marrow rescue is assured.
Bone marrow Transplantation leads to 5 year survival of 50 to 70% when used in first remission of AML, and ALL. This result is better than the best conventional chemotherapy. It is therefore standard of care in the United States. In Non Hodgkin Lymphoma, transplantation is most indicated when there is evidence of Marrow involvement.
Autologous transplantation is primarily used with Myeloma in the United States, although it is also used in
1.Non Hodgkin lymphoma and in recurrent germ cell cancers (Testicular) and in Neuroblastoma,
2.Myeloma.
3. but also AML and ALL.
Depletion of T cell in the marrow is used decrease graft-Vesus Host effect in allogeneic BM transplantation, while the use of Automated direct sequencing allow the discovery of more secondary HLA mismatch which improves unrelated donor selection.
Tumor contamination and lack of GVHD makes autologous transplant less effective. Researchers are looking to better detect contamination and may be develop eradication methods to improve results of Autologous transplant!
Relapse after transplant can respond to
1.Cessation of immuno-suppressant if it was on them in Hematologic cancers
2.Reinfusionn of donor lymphocytes (often after reinduction chemotherapy)
3.Reduce-intensity allogeneic retreatment
4.or 2nd full transplant if the progression free survival was over a year
5.some new target therapy!
GVHD, Veno-Occlusive Hepatic disease and infections plague transplantation, particularly the allogeneic type, makes this procedure risky ! (read also Frederic Appelbaum)
(The CRBCM is in the process of acquiring a PCR light Cycler...research will advance at CRBCM)
Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As the survival of the procedure increases, its use has expanded beyond cancer, such as autoimmune diseases.[1][2] wikipedia
==================================================================
Around the World over 50,000 Bone marrow transplants occur now each year. Bringing cure to many lives. When it is allogeneic, the graft-versus tumor effect prolongs the cancer killing...yielding better cure rates, sometime at the risk of graft versus host disease that requires careful management. In most leukemia, Allogeneic transplant is the only curative option (CML). Transplant can also restore immuno-deficiency in congenital syndromes such as the Wiskott-Aldrich Syndrome and the severe combined deficiency-immunodeficiency syndrome.
When the risk is reasonable, transplant has been indicated to:
1.Restore defectuous Red Blood Cells (Aplastic Anemias, Thalassemias,
2.Restore deficient enzymatic and metabolic diseases (Gaucher disease)
3.fight malignancies by allowing to use high doses of both Radiation and chemotherapy when Marrow rescue is assured.
Bone marrow Transplantation leads to 5 year survival of 50 to 70% when used in first remission of AML, and ALL. This result is better than the best conventional chemotherapy. It is therefore standard of care in the United States. In Non Hodgkin Lymphoma, transplantation is most indicated when there is evidence of Marrow involvement.
Autologous transplantation is primarily used with Myeloma in the United States, although it is also used in
1.Non Hodgkin lymphoma and in recurrent germ cell cancers (Testicular) and in Neuroblastoma,
2.Myeloma.
3. but also AML and ALL.
Depletion of T cell in the marrow is used decrease graft-Vesus Host effect in allogeneic BM transplantation, while the use of Automated direct sequencing allow the discovery of more secondary HLA mismatch which improves unrelated donor selection.
Tumor contamination and lack of GVHD makes autologous transplant less effective. Researchers are looking to better detect contamination and may be develop eradication methods to improve results of Autologous transplant!
Relapse after transplant can respond to
1.Cessation of immuno-suppressant if it was on them in Hematologic cancers
2.Reinfusionn of donor lymphocytes (often after reinduction chemotherapy)
3.Reduce-intensity allogeneic retreatment
4.or 2nd full transplant if the progression free survival was over a year
5.some new target therapy!
GVHD, Veno-Occlusive Hepatic disease and infections plague transplantation, particularly the allogeneic type, makes this procedure risky ! (read also Frederic Appelbaum)
(The CRBCM is in the process of acquiring a PCR light Cycler...research will advance at CRBCM)
Subscribe to:
Posts (Atom)